The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects
Open accessAbstract
Purpose: Methotrexate plasma concentration is related to its clinical effects. Our aim was to identify the genetic basis of interindividual variability in methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia (ALL). Patients and Methods: We performed a genome-wide analysis of 500,568 germline single-nucleotide polymorphisms (SNPs) to identify how inheritance affects methotrexate plasma disposition among 434 children with ALL who received 3,014 courses of methotrexate at 2 to 5 g/m 2. SNPs were validated in an independent cohort of 206 patients. Results: Adjusting for age, race, sex, and methotrexate regimen, the most significant associations were with SNPs in the organic anion transporter polypeptide, SLCO1B1. Two SNPs in SLCO1B1, rs11045879 (P = 1.7 × 10−10) and rs4149081 (P = 1.7 × 10−9), were in linkage disequilibrium (LD) with each other (r 2= 1) and with a functional polymorphism in SLCO1B1, T521C (rs4149056; r 2> 0.84). rs11045879 and rs4149081 were validated in an independent cohort of 206 patients (P = .018 and P = .017), as were other SLCO1B1 SNPs residing in different LD blocks. SNPs in SLCO1B1 were also associated with GI toxicity (odds ratio, 15.3 to 16.4; P = .03 to .004). Conclusion: A genome-wide interrogation identified inherited variations in a plausible, yet heretofore low-priority candidate gene, SLCO1B1, as important determinants of methotrexate's pharmacokinetics and clinical effects.
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Cites
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Genomewide Association Analysis of Coronary Artery Disease
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Cited by
Inaba, H., Greaves, M., & Mullighan, C. G. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62187-4 · Cited by 1,074
Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia
Bhojwani, D., Sabin, N. D., Pei, D., Yang, J. J., Khan, R. B., Panetta, J. C., Krull, K. R., Inaba, H., Rubnitz, J. E., Metzger, M. L., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.0808 · Cited by 400
Self-citationMeyer, U. A., Zanger, U. M., & Schwab, M. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100502 · Cited by 157
Impact of genetic variation in OATP transporters to drug disposition and response
Gong, I. Y., & Kim, R. B. (2013) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-12-rv-099 · Cited by 137
Implementation and utilization of genetic testing in personalized medicine
Scott, S., Abul-Husn, N., Owusu Obeng, A., Sanderson, S., & Gottesman, O. (2014) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s48887 · Cited by 106
Metadata
- Authors
- Treviño, L. R., Shimasaki, N., Yang, W., Panetta, J. C., Cheng, C., Pei, D., Chan, D., Sparreboom, A., Giacomini, K. M., Pui, C.-H., Evans, W. E., & Relling, M. V.
- Venue
- Journal of Clinical Oncology
- Published
- 2009-12-10
- Volume
- 27
- Issue
- 35
- Pages
- 5972-5978
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2038526706
- Cited by
- 349
- References
- 7
- FWCI
- 18.07
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Treviño, L. R., Shimasaki, N., Yang, W., Panetta, J. C., Cheng, C., Pei, D., Chan, D., Sparreboom, A., Giacomini, K. M., Pui, C.-H., Evans, W. E., & Relling, M. V. (2009). Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2008.20.4156
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